Abstract

The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP. The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias. Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STVICD) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STVRV,EGM/LV,MAPD). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STVICD threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STVICD threshold was reached. In experiment 1, 8 of 8 dogs had repetitive TdP, and STVICD increased from 0.96 ± 0.42 ms to 2.10 ± 1.26 ms (P <.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STVRV,EGM/LV,MAPD from 2.02 ± 1.12 ms to 0.78 ± 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs. STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias.

Highlights

  • The implantable cardioverter-defibrillator (ICD) has gained a pivotal role in the management of ventricular arrhythmias since landmark trials showed improvement in primary and secondary

  • High-rate pacing (HRP) decreased STVRV,EGM/left ventricular (LV),monophasic action potential duration (MAPD) from 2.02 6 1.12 ms to 0.78 6 0.28 ms, which was accompanied by prevention of torsades de pointes (TdP) in 7 of 8 dogs

  • After cessation of HRP, 8 of 8 dogs showed recurrent TdP, confirming that the dose of dofetilide was sufficient to cause a proarrhythmic state. This proof-of-principle study confirms 3 earlier findings but with use of an ICD equipped with an algorithm to automatically determine short-term variability (STV) and activate HRP once the STV threshold is reached: (1) ventricular arrhythmias are preceded by an increase in STV; (2) HRP is highly effective in preventing ventricular arrhythmias and can be guided by STV; and (3) HRP achieves prevention by decreasing the repolarization parameter STV

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Summary

Introduction

The implantable cardioverter-defibrillator (ICD) has gained a pivotal role in the management of ventricular arrhythmias since landmark trials showed improvement in primary and secondary. The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP

Methods
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Conclusion

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